A retrospective, real-world study (N = 304) of the use of bevacizumab biosimilar (Mvasi, Amgen) in patients with metastatic colorectal cancer (mCRC) suggests physicians are comfortable prescribing the biosimilar in accord with historical use of the reference product (Avastin, Genentech), according to data presented at the 

ASCO Gastrointestinal Cancers Symposium 2021

Investigators based that conclusion on evidence that patients who received bevacizumab biosimilar in the first line of treatment for mCRC had demographic and clinical characteristics similar to those for patients treated with the reference product.

In addition, they said, among patients who had prior treatment with bevacizumab reference product (n = 162), most received the biosimilar in the first line of treatment within 28 days, which indicated the switch to biosimilar treatment occurred within the same line of therapy.

Bevacizumab is administered intravenously and works by starving tumors of nourishment by counteracting a protein (vascular endothelial growth factor) that enables tumors to develop blood vessels. Avastin was approved by the FDA in 2006 and European Medicines Agency (EMA) in 2009. 

 launched in July 2019 in the United States and was the first biosimilar to Avastin to gain FDA approval.

The biosimilar’s approval was based on a comparative clinical study in non-squamous non–small cell lung cancer, the researchers examined real-world use of bevacizumab biosimilar in mCRC, an approved indication they said is “lacking clinical trial data.”

They identified 304 eligible patients using a database of US electronic medical records from ConcertAI. The patients were adults with a diagnosis of mCRC who had been treated with bevacizumab biosimilar the first year after the product launch.

The respective divide between patients treated at community cancer centers as opposed to academic institutions was 86% vs 14%, respectively. Investigators said 57% of patients treated at community centers had prior bevacizumab compared with 31% of patients at academic centers.

Just over half (53%) of the entire patient cohort had previously received treatment with the reference product. The majority of patients received tumor-marking genetic tests and 53% of tumors had 

 mutations. The vast majority of tumors were negative for 

 mutations (92% and 86%, respectively). Microsatellite instability (MSI) and mismatch repair (MMR) testing indicated 93% of patients were MSI stable and 93% were MMR proficient.

Demographic characteristics and clinical characteristics, such as Eastern Cooperative Oncology Group performance status, tumor grade, comorbidities, and disease stage at diagnosis, were “comparable” between the 2 groups, according to the authors. Diabetes, chronic obstructive pulmonary disease, and renal disease were the most frequent comorbidities in both groups.

Investigators said 74% of patients who had prior bevacizumab treatment received bevacizumab biosimilar within 28 days of their last treatment with the reference product. Most (83%) experienced no disease progression between their last treatment with the reference product and starting treatment with bevacizumab biosimilar.

The study was conducted with Amgen funding.

DeClue RW, Rhodes W, Accortt NA, et al. Demographics and clinical characteristics of metastatic colorectal cancer patients treated with bevacizumab-awwb in real-world oncology clinics. Presented at: ASCO GI Cancers Symposium 2021; January 15-17, 2021. Accessed January 29, 2021. https://meetinglibrary.asco.org/record/194175/abstract

Articles

Investigators noted comparable use of bevacizumab biosimilar and reference products among patients treated for metastatic colorectal cancer (mCRC). 

Study: Bevacizumab Biosimilar Finds Acceptance in First-Line Treatment of mCRC

Tony Hagen is senior managing editor for The Center for Biosimilars

The past year was “turbulent” for the health care industry, and sales of Coherus BioSciences' pegfilgrastim product (Udenyca) were not what the company had hoped. But as the pandemic wanes, the company anticipates a change in market dynamics that will enable the product to achieve greater market share, according to Dennis M. Lanfear, president and CEO of the Redwood City, California, company.

Udenyca launched in 2019 and has achieved a roughly 20% share of the pegfilgrastim market, Lanfear said in a presentation at the 39th Annual JP Morgan Global Healthcare Conference. Coronavirus disease 2019 (COVID-19) gave a rival product a boost that denied Udenyca a greater share of the market it might otherwise have attained, he said. Pegfilgrastim is used to fight off infection associated with chemotherapy treatment. 

Amgen’s Neulasta Onpro on-body injector, launched in 2015, enables patients to receive pegfilgrastim injections at home, saving them from having to visit clinics battling to prevent the spread of COVID-19. By midyear 2020, Onpro had accumulated a 58% 

In his presentation at this year's virtual J.P. Morgan Health Care Care Conference, Lanfear predicted that vaccinations will enable patients to return to clinics for vaccinations and use of the Onpro will diminish, creating market opportunity for Udenyca. 

The chief value of Onpro is its convenience for home use, although a recent study recorded 

 from 1.7% to 6.9%. “We expect that as COVID-19 wanes, market gains at the expense of [the] Onpro share are expected to resume,” Lanfear said.

From its launch in January 2019 until September 30, 2020, Udenyca has achieved $720 million in revenues, Lanfear said. There are now 4 pegfilgrastim biosimilars on the market; most recently, Pfizer’s Nyvepria was launched in December 2020. Amgen’s originator pegfilgrastim products, including Onpro, control about 70% of the market. Although Lanfear predicted that Udenyca’s sales growth curve would point upward more sharply in 2021, he acknowledged the market power of the on-body injector and indicated that Coherus is working on its own version. He said it would be premature to share an anticipated market entry date.

In a discussion of the company’s biosimilar pipeline of products, Lanfear noted the company is developing versions of ranibizumab and aflibercept, both of which are for treatment of macular degeneration. Their respective originator brands are Lucentis and Eylea. The markets for each of these products are about $3 billion, Lanfear said.

Coherus is also developing a biosimilar to adalimumab (reference, Humira), which he said would likely enter the market in December 2023. The biologic is for treatment of rheumatologic and gastrointestinal disorders. Coherus submitted its biologics license application for FDA approval of its adalimumab biosimilar candidate (CHS-1420) at the end of 2020, and assuming regulatory approval, a 

The adalimumab market is changing, with providers starting to use citrate-free, high-concentration versions of this product, which may complicate marketing plans for Coherus and other biosimilar producers.

According to Lanfear, Humira achieved US sales of $15.9 billion in 2020. AbbVie, the originator company, has employed its exclusivity advantage to impose a steady stream of adalimumab price hikes. Humira prices have climbed 6-fold since 2005, according to Lanfear’s presentation.

“Relentless Humira price hikes and payer expense burden create a pent-up demand for biosimilar alternatives,” he said, predicting a “massive decoupling” ahead that would shift supply contracts to biosimilar manufacturers, once biosimilar versions of adalimumab become available in the United States, in 2023.

In a description of Coherus’ marketing strategy for leveraging greater biosimilar revenues, Lanfear said Coherus would target payers most of all, because they have the greatest control over what biologics are used by the health care community, relative to specialty pharmacies, providers, and patients. “We expect payers to have a significant share of power in selecting products and to drive share away from originators if properly incentivized.”

Coherus also has a bevacizumab biosimilar candidate (reference, Avastin) that it is developing in partnership with Innovent Biologics to submit for regulatory approval in the second half of 2021, Lanfear said. Bevacizumab is for the treatment of various types of cancer, including colorectal, lung, and kidney.

Annual J.P. Morgan Healthcare Conference

Coherus BioSciences CEO Dennis M. Lanfear discusses the company's biosimilar marketing prospects in 2021.

Coherus CEO Discusses Post–COVID-19 Growth Prospects

Results were inconclusive in a study of hypertension and proteinuria in 75 patients treated with bevacizumab reference vs biosimilar products, investigators reported at the ASCO Gastrointestinal Cancers Symposium 2021.

They compared incidence of hypertension and proteinuria in patients treated with various chemotherapy regimens in combination with bevacizumab. Investigators evaluated reference bevacizumab (Avastin) vs 2 biosimilars introduced on the US market starting in 2019: Mvasi, first marketed in July 2019, and Zirabev, first marketed in January 2020. The study period extended from January 2019 to July 2020 and enrolled patients with gastrointestinal cancer at Roswell Park Comprehensive Cancer Center at Buffalo, New York.

“Early recognition of uncontrolled blood pressures and worsening kidney function is needed to prevent delayed intervention,” investigators said, recommending routine monitoring of hypertension and proteinuria following treatment with bevacizumab.

Bevacizumab is a recombinant humanized monoclonal antibody that targets the development of blood vessels that support the growth of tumors. Hypertension and proteinuria, which can lead to pulmonary edema and affects kidney health, are adverse events of bevacizumab.

Investigators noted a higher risk of hypertension in the reference bevacizumab group (52.4% vs 36.4%), although this was not statistically significant (

 = .2427). They observed hypertension in patients after a median of 5 doses of reference bevacizumab vs 1.5 doses of bevacizumab biosimilar (

Investigators observed a higher risk of proteinuria for patients treated with reference bevacizumab vs bevacizumab biosimilar (35.7% vs 30%), although this difference was not statistically significant (

 = .7193). However, proteinuria occurred later in the treatment cycle with reference bevacizumab than with bevacizumab biosimilar (median, 213 days vs 53.5 days following the first bevacizumab dose; 

Investigators concluded that the incidence of hypertension and proteinuria in patients treated with reference vs biosimilar bevacizumab requires study in larger patient cohorts.

Man Y, Yu H, Mukerjee S, Zalewski O. Incidence of hypertension and proteinuria in patients treated with bevacizumab versus bevacizumab biosimilar. Presented at ASCO GI Cancers Symposium 2021; January 15-17, 2021. Accessed January 19, 2021. 

https://meetinglibrary.asco.org/record/194106/abstract

ASCO GI 

The study was designed to elucidate incidence of hypertension and proteinuria in patients treated with bevacizumab reference vs biosimilar products. 

Investigators Study Risks of Hypertension, Proteinuria With Bevacizumab

Investigators have demonstrated that initial uptake of the first bevacizumab biosimilar (Mvasi, Amgen) in the United States was strongest for patients receiving treatment for metastatic colorectal cancer (mCRC).

 at the ASCO Gastrointestinal Cancers Symposium 2021, investigators sought to evaluate uptake of Mvasi, which was approved by the FDA for all indications of the reference product (Avastin): mCRC, cervical cancer (CC), non–small cell lung cancer (NSCLC), glioblastoma (GBM), and metastatic renal cell carcinoma (mRCC).

They also concluded that, based on the findings, providers were comfortable initiating or transitioning patients to the bevacizumab biosimilar, and they saw little difference in patient characteristics or demographics between those who previously received the reference product and those who initiated treatment with the bevacizumab biosimilar.

The investigators drew patient data from a Flatiron Health electronic health records database,  Oncology Services Comprehensive Electronic Records, which included cancer treatment information for 2.2 million patients from over 280 cancer clinics. The study included patients who received a bevacizumab biosimilar infusion between July 2019, when Mvasi was first approved, and April 2020 (9 months).

The bevacizumab biosimilar was first used in a patient with mCRC, and this occurred within 10 days of product launch. Ultimately, during the study period, 68% of patients with mCRC received an infusion of Mvasi. The other indications accounted for lower biosimilar use: NSCLC, 14%; GBM, 11%; CC, 5%; and mRCC, 1% (

Patients eligible for inclusion numbered 1657, among whom 685 had no prior reference drug treatment vs 972 who did. The investigators said 49% of patients (810) were younger than 65 years, and 60% were White; 11%, Black; and 2%, Asian. The race distribution between those with no prior reference drug and prior reference drug was equivalent, 84% of patients had Eastern Cooperative Oncology Group (ECOG) scores of 0/1, and median body weight was 78 kg. ECOG is a measure of a patient’s ability to function independently, with 0 representing the highest functioning patients and 5 indicating deceased.

The investigators said 59% of patients with mCRC received the reference product prior to receiving the biosimilar. Among other tumor types, the respective percentages ranged from 42% to 50%.

For 67% of patients with mCRC, the average length of time that elapsed between the last reference drug infusion and biosimilar initiation was ≤ 28 days.

A second bevacizumab biosimilar (Zirabev, Pfizer) was launched in the United States in January 2020. Mvasi was 

at a 15% discount to the reference drug wholesale acquisition cost (WAC; $677 vs $797, respectively) and a 12% average sales price discount (ASP; $677 vs $767). Zirabev was launched at 23% and 19% WAC and ASP discounts, respectively ($613 vs $797 and $613 vs $761, respectively). These sales data, provided in a 2020 report from Amgen, reflect the early 2020 launch of Zirabev and the changes in ASP and WAC that occurred since Mvasi was launched in the third quarter of 2019. 

As of the second quarter of 2020, Mvasi had attained a 38% market share in the United States vs 2% for Zirabev.

Jin R, Accortt NA, Sandschafer D, Lawrence T, Loaiza-Bonilla A. Initial experience of patients treated in a real-world clinical setting with bevacizumab-awwb: the first FDA-approved biosimilar to bevacizumab. Presented at: ASCO GI Cancers Symposium; January 15-17, 2021. Accessed January 15, 2021. https://meetinglibrary.asco.org/record/194163/poster

Investigators looked at the first 9 months of use following the launch of the bevacizumab biosimilar Mvasi to gauge physician comfort with this agent across tumor types.

Swift Uptake for Mvasi Suggests Provider Comfort With Use

Rapid health care reforms in China have led to a regulatory environment that improves conditions for biosimilar development and approval, according to Lawrence A. Hill, PharmD, MBA, RPh, BCPS. Hill is CEO of Gan & Lee Pharmaceuticals, a company specializing in the development and marketing of insulin products in Asia.

Hill, who spoke at the recent Festival of Biologics virtual meeting, said that biosimilars and China go well together because the country has a large “copy” culture in medicine. The country has 382 biologic drugs and vaccines, and just 21 of those are innovative or originator products, he said.

China has supercharged the growth of its biologics industry with a massive health care reform begun in 2008. In 2003, according to the Chinese Ministry of Health, just 55% of urban residents and 21% of rural residents in China had insurance 

. The reform program boosted coverage to 97% of individuals by 2015; however, according to Hill, many of the most expensive medicines still must be paid out-of-pocket. The difficulty many residents of China have in paying for modern medicine makes this a very price sensitive market, which also improves the potential for biosimilar uptake, owing to their cost advantages, he said.

Biosimilars are considered an “integral part” of China’s effort to achieve universal coverage, with the first biosimilar, for rituximab, approved in February 2019. The country has a population of 1.3 billion and its biologics market was the second largest by sales in 2017. This market is also growing fast, with a 16% compound annual growth rate (CAGR) from 2010 to 2021. The market for copy biologics is growing at a 25% CAGR, Hill said.

As a result of the modernization effort, China’s regulatory system for drugs is rapidly coming to resemble the frameworks that have been established in the United States and European Union, Hill said. Priority review for drugs with exceptional clinical value was established in 2016, followed in 2017 by many guidelines for easing acceptance of imported drugs, conditional approvals of urgently needed drugs, and an “orange book” for generic product standards.

Regulatory enhancements from 2018 cover fast approvals for urgently needed foreign drugs. “Companies that can provide evidence of a drug working equally well across races can immediately apply for marketing approval with existing data and be eligible for priority review,” Hill said. Guidelines for accepting overseas clinical trial data and a shortening of the regulatory review period leading to drug approval also came about in 2018. Companies can even move forward with clinical trials if China’s Center for Drug Evaluation (CDE) does not meet preset deadlines for responding with comments, Hill noted.

In 2015, the CDE published final technical guidance for the development and evaluation of copy biologicals. This established principles for research, development, and evaluation of biosimilars, and it defines a biosimilar along lines almost identical to those accepted in the United States and Europe, namely that the drug must be similar in quality, safety, and efficacy and should have an  amino acid sequence that is identical to the originator product.

There are some key differences. Chinese authorities almost always require a comparative clinical efficacy study for a biosimilar, something that regulators may request in the United States or European Union but which in those regions is increasingly considered of little value compared with other biosimilar development groundwork, such as structural and functional characterization and comparative analytical, nonclinical, and clinical stepwise evaluation.

China will not accept a reference product that has been approved by foreign regulators. By comparison, US regulators may accept a foreign reference product if bridging studies are done to demonstrate biosimilarity. There is no established interchangeability policy in China for the substitution of biosimilars for reference products at the pharmacy counter, and the country has no specific standard for biosimilar naming. In the United States, a system of suffixes is applied to approved biosimilars to aid in drug identification and real-world performance tracking.

“The biosimilar regulatory environment in China has been evolving extremely rapidly,” Hill concluded. This has occurred against a backdrop of “exceptionally aggressive” modernization of the pharmaceutical regulatory environment.

Entering the market is challenging for foreign companies, and Hill said the only route of entry for a foreign concern is to partner with a local biopharmaceutical company that can provide guidance and the sponsorship needed for foreign applications. “There are exceptional commercialization opportunities within China. Foreign products are being welcomed,” he said.

Amgen, of Thousand Oaks, California, is one of the outside companies that has taken the 

 of local sponsorship. In 2017, the company partnered with Simcere of Nanjing, China, to codevelop and distribute biosimilars in China for patients with cancer and inflammatory diseases. And in 2019, Samsung Bioepis, of Incheon, Republic of Korea, 

 with the Chinese biopharmaceutical company 3SBio to develop and commercialize biosimilars, including SB8, a bevacizumab biosimilar referencing Avastin.

Some Chinese companies are becoming biosimilar pioneers in their own right. These include Henlius, Innovent, Bio-Thera, and Hisun Pharmaceuticals. Henlius obtained the first biosimilar approval in China and has a large pipeline of products. The company most recently reported Chinese regulatory acceptance for HLX03, an 

 biosimilar for the treatment of rheumatoid arthritis, ankylosing spondylitis, and plaque psoriasis. This marks the third biosimilar approval in China for Henlius.

Hill’s company, Gan & Lee, was founded as Beijing Gan & Lee Biotechnology and developed the first recombinant human insulin (Gansulin) in China.

Festival of Biologics Basel

Lawrence A. Hill, PharmD, MBA, RPH, BCPS, provided an insider's view of the rapidly changing biologics and biosimilars market and regulatory structure in China. 

Hill Describes Supercharged Biologics Market in China

Investigators have reported pharmacokinetic (PK) findings that confirm the biosimilarity of Viatris’ trastuzumab biosimilar candidate (MYL-14010, Ogivri) to reference Herceptin. Ogivri, developed by Mylan, which is now Viatris, was approved by the FDA in 2017.

 randomized phase 3 study, which previously demonstrated comparable efficacy and safety for Ogivri vs Herceptin as frontline treatment for women with human epidermal growth factor receptor 2 (HER2)–positive advanced breast cancer. The biosimilar was launched in the United States in December 2019, and these latest findings were presented at the 2020 San Antonio Breast Cancer Symposium (SABCS).

Patients (N = 485) were randomized to receive the biosimilar (n = 245) or reference product (n = 240) in combination with a taxane (docetaxel or paclitaxel) every 3 weeks for 24 weeks for 8 cycles, followed by additional cycles of monotherapy until disease progression, discontinuation, or unacceptable toxicity.

Primary objectives of the study were to compare drug concentration variation (area under the curve), maximum serum drug concentration, clearance (drug elimination), drug propensity to leave the plasma (volume of distribution), and terminal elimination half-life (no further drug distribution or absorption).

The investigators also sought to assess shed extracellular domain (ECD) HER2 receptor fragments and their effect on PK parameters. The decrease of shed ECD HER2 fragments is associated with an improved prognosis in metastatic breast cancer.

They took PK samples from patients at cycles 1, 2, 4, 6, 8, and 9 (monotherapy) to assess minimum serum concentrations. Serum maximum concentration samples were collected at the end of cycles 1 and 6. Additional samples were collected from a population subset. The final analysis included 213 patients in the biosimilar group and 202 in the Herceptin group.

No notable differences in demographics were observed between the 2 patient cohorts, the investigators said, noting there were no dissimilarities in trastuzumab concentrations between the groups. Treatment (biosimilar or reference) was not a significant covariate of clearance (

However, ECD HER2 concentration was a significant factor in trastuzumab clearance, and weight was also a significant covariate of clearance and drug distribution (volume of the central compartment).

In the trough concentration (lowest drug concentration before the next dose) analysis, data were comparable between treatment arms at the end of cycles 1 and 6, the investigators said (

They used Bayesian statistics to evaluate steady state drug exposure between treatment arms and found comparable results indicating PK biosimilarity between the biosimilar and reference drugs. Steady state represents equivalent rates of drug absorption and elimination.

A low frequency of antidrug antibodies, which counteracts the effects of trastuzumab, were observed between Ogivri (n = 14) and Herceptin (n = 21).

Investigators concluded the population PK profiles of Ogivri vs Herceptin were comparable in patients with HER2-positive metastatic breast cancer. They said the study confirmed earlier PK findings.

Financial support for the study and its presentation at SABCS was provided by Viatris, investigators said.

Owen J, Rackley R, Liu M, et al. Population pharmacokinetics of MYL-14010 (a trastuzumab biosimilar) and reference trastuzumab (Herceptin) in patients with HER2-positvie metastatic breast cancer. Poster presented at: SABCS; December 8-11, 2020. PS18-23. https://sabcs.onlineeventpro.freeman.com/single-file-viewer/25581567

San Antonio Breast Cancer Symposium

Pharmacokinetic (PK) parameters matched up with those of reference trastuzumab in an extended analysis of data from the HERITAGE trial. 

Data From HERITAGE Confirm PK Biosimilarity for Ogivri

A study of the trastuzumab biosimilar ABP 980 (Kanjinti) in Europe found strong uptake patterns, according to an abstract presentation at the 2020 San Antonio Breast Cancer Symposium.

ABP 980 is approved in Europe and the United States for the treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer and metastatic gastric cancer. Investigators sought to understand the real-world application of this product in clinical treatment of patients with breast cancer.

They enrolled patients 18 years or older with a history of breast cancer of any disease or treatment phase, seeking primarily to understand patient demographics and disease characteristics. Exploratory end points included cardiac dysfunction, infusion-related problems, other adverse events, and other safety issues. Efficacy  was a secondary end point.

Enrollment included 135 women from Poland, Italy, the Netherlands, France, and Spain, mostly from hospital sites, both academic and public or private. The mean patient age was 58.3 years. 

The investigators said 28% of sites had policies on biosimilar use and that 36% of patients were informed they were being started on a biosimilar, with 34% being notified what brand of biosimilar would be used. Twenty-two percent, 27%, 13%, and 28% of patients had stage I, II, III, or IV disease, respectively, at the time ABP 980 was initiated. They also said 68% of patients had estrogen/progesterone receptor–positive tumors. All patients (n = 73) who had been evaluated for Eastern Cooperative Oncology Group performance  had a score of 0 or 1.

There was roughly equal use of ABP 980 across treatment settings: neoadjuvant, 39%; adjuvant 30%; and metastatic, 30%.

Among patients who received treatment for metastatic breast cancer (n = 41), 56% and 20% received it for frontline and second-line treatment, respectively. The investigators said that 40% (n = 54) of patients switched to ABP 980 from another trastuzumab product. Of those, 44% switched from the intravenous form of the originator biologic and 15% switched from the subcutaneous form. Most who switched to the subcutaneous form were receiving treatment for metastatic disease.

The investigators concluded there was ABP 980 “uptake across a mixture of institution types and breast cancer treatment settings, including those with curative potential.” The study is ongoing.

Kufel-Grabowska J, San T, Bernardo A, et al. Patterns of use of a trastuzumab biosimilar (ABP 980) in patients with HER2+ breast cancer treated in clinical practice in Europe: An interim analysis from an observational chart review study (GARDENIA). Poster presented at: San Antonio Breast Cancer Symposium; December 8-11, 2020. PS10-50. 

Among patients treated for metastatic breast cancer, 40% switched to ABP 980. 

Investigators Chart ABP 980 Biosimilar Uptake in European Clinics

Investigators studying trastuzumab biosimilar savings and use rates across different disease settings in human epidermal growth factor receptor 2 (HER2)-positive breast cancer observed dramatically increased usage of biosimilars and said payer policy appears to have contributed to higher biosimilar utilization.

They looked at treatment plans submitted for patients to determine usage rates for originator vs biosimilar trastuzumab and trastuzumab in combination with hyaluronidase-oysk. The average costs of originator and biosimilar trastuzumab per patient cycle were $4502 and $3618, respectively, with an average savings per biosimilar dose (440 mg, trastuzumab; 600 mg trastuzumab hyaluronidase) of $884. Total savings for 4502 patients with stage I to III disease was $24.4 million, according to the 

 presentation at the 2020 San Antonio Breast Cancer Symposium (SABCS).

Of 6657 treatment plans submitted for 4505 patients with stage 0 to III disease, the biosimilar usage rate was 34% (n = 2271 treatment plans). Investigators said that for 3312 plans submitted for 1933 patients with stage IV/recurrent disease, the biosimilar usage rate was 27% (n = 904 treatment plans).

The treatment plan submissions were tracked from June 2019 to October 2020 and showed a dramatic increase in biosimilar adoption. For patients with stage I to III disease, trastuzumab biosimilar use was 1.4% in the third quarter of 2019 vs 65.9 % in the fourth quarter of 2020. For patients with stage IV/recurrent disease, usage climbed from 1.6% to 49.3%, respectively.

Some patients had multiple treatment plans based on receipt of adjuvant or neoadjuvant therapy, treatment for local or recurrent disease, or metastatic/recurrent therapy. Patients with stage I to III disease were assumed to receive 1 year (18 doses) of trastuzumab therapy. Those with stage IV/recurrent disease were assumed to receive 11 months (16 cycles) of treatment.

The investigators said there was evidence that biosimilar use increased based on payer policies that favored biosimilars. Biosimilar use was 41.5% where payer policies were favorable vs 30.9% when that was not the case.

”As biosimilars were being introduced at different times during this time period and payer policy would likely lag behind these introductions, it is likely that the observed difference in biosimilar use by payer policy is underestimated,” the authors of the study wrote.

They concluded that the potential savings from biosimilar trastuzumab in breast cancer are “significant. Future estimates should use more rigorous models with stratification by use with hormonal therapy, chemotherapy, combinations with pertuzumab, or single agent, and the corresponding durations of therapy,” the authors recommended.

Flood WA, Avery T, Kozlovsky V, Margolis N, Reddy SK. Real world data on the adoption of trastuzumab biosimilars in the treatment of HER2-positive breast cancer. Poster presented at: SABCS; December 8-11, 2020. PS9-63. https://sabcs.onlineeventpro.freeman.com/single-file-viewer/25582299

In little over 1 year of use in patients with breast cancer, trastuzumab biosimilars have seen rapid growth in uptake. 

Investigators Demonstrate Dramatic Rise in Trastuzumab Biosimilar Use

Studies of trastuzumab biosimilars in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) have yielded significant findings, according to presentations at the 2020 San Antonio Breast Cancer Symposium.

Investigators achieved a 45.5% response rate in patients with HER2-positive mBC and 

 aberrations who were treated with the trastuzumab biosimilar Herzuma and an experimental PIK3CA pathway inhibitor (gedatolisib, PF-05212384) in a phase 2 pilot trial.

 pathway aberrations tend to promote tumor cell growth and survival despite treatment with monoclonal antibodies, chemotherapy, and radiotherapy. The study authors hypothesized the combination of trastuzuamb and gedatolisib would improve outcomes for select patients with disease progression who had exhausted approved treatment options for mBC.

They enrolled 15 patients with HER2-positive mBC with a known 

) and who had failed on multiple prior lines of therapy. Patients received a trastuzumab biosimilar 8 mg/kg intravenously for the first cycle and then 6 mg/kg every 3 weeks plus gedatolisib 180 mg on days 1, 8, and 15 every 21 days.

As of the data cutoff on August 4, 2020, 11 patients were eligible for response assessment. Five achieved partial response as their best response; 3, stable disease; and 3, progressive disease. All patients with partial response remain on the investigational treatment, with the longest term being 7.8 months. Among the patients with stable disease, 1 discontinued due to disease progression and 2 continue to receive therapy. The investigators said the disease control rate was 72.7% with no treatment-related fatal adverse events.

A multicenter, global, phase 3 study of the trastuzumab biosimilar MYL-1401O (Ogivri) in patients with HER2-positive mBC has demonstrated pharmacokinetic (PK) equivalence between the biosimilar and the reference product (Herceptin).

by the FDA in December 2017 and marketed in the United States December 2019.

Investigators randomized 485 patients 1:1 to receive the biosimilar or reference product, with the aim of assessing biosimilarity on the basis of efficacy, safety, population PK, and immunogenicity. They said 482 patients were included in the population PK analysis.

The measures for drug exposure at or near steady-state dosing were comparable for Ogivri and the reference drug, demonstrating PK biosimilarity, the investigators said. Steady state is the time the concentration of the drug in the body stays consistent during administration, with the amount of drug entering the patient’s system being equivalent to the rate of elimination.

Other measures of PKs also supported equivalence, they said. “Population PK profiles of [Ogivri] vs Herceptin were similar in patients with HER2-positive mBC. Model-based exposure measures were similar between treatments.”

They added that extracellular domain fragments of the HER2 receptor “were a strong determinant of trastuzumab clearance [elimination], and clearance was similar between [biosimilar and reference drug] treatments.” They observed that trough concentrations—drug concentrations immediately before the next dose—were similar between treatments at the end of cycle 1 and at cycle 6.

1. Kim JW, Ahn HK, Choi JG, et al. Phase II pilot study of trastuzumab biosimilar (Herzuma) plus gedatolisib in patients with HER-2 positive metastatic breast cancer who progressed after 2 or more HER-2 directed chemotherapy [KM-10A/KCSG18-13 interim analysis]. Presented at: SABCS; December 8-11, 2020. Abstract PS11-39. www.sabcs.org/portals/sabcs2016/2020%20SABCS/Final%20PDF%20Docs%20111620_All%20PDF%20File%20No%20Embargoed%20Abstracts.pdf

2. Owen J, Rackley R, Liu M, et al. Population pharmacokinetics (pop PK) of MYL‑1401O (a trastuzumab biosimilar) and reference trastuzumab (Herceptin) in patients with HER2‑positive metastatic breast cancer (mBC). Presented at: SABCS; December 8-11, 2020. Abstract PS18-23. www.sabcs.org/portals/sabcs2016/2020%20SABCS/Final%20PDF%20Docs%20111620_All%20PDF%20File%20No%20Embargoed%20Abstracts.pdf

Two studies of trastuzumab biosimilars have improved understanding of these medicines as monotherapy and in combination with other agents in metastatic breast cancer.

Trastuzumab Biosimilar With PIK3CA Inhibitor Shows Efficacy in Advanced Breast Cancer

Investigators hope to improve durability of response in human epidermal growth factor receptor 2 (HER2)-positive solid tumors with a novel trastuzumab biosimilar conjugated to a toll-like receptor 7/8 agonist and designed to activate myeloid antigen presenting cells, which alert T cells to the presence of cancerous cells and mediate an immune response.

The investigational biosimilar (BDC-1001) holds potential as an improvement on anti-HER2 monoclonal antibodies in HER2-driven or -expressing cancers. In studies of mice with tumors resistant to conventional treatment, trastuzumab-based immune-stimulating antibody conjugates have elicited potent and durable antitumor efficacy “including complete tumor regression,” investigators said in an 

 presented at the 2020 San Antonio Breast Cancer Symposium.

“Importantly, BDC-1001 did not induce interstitial lung disease, cytokine release syndrome, or thrombocytopenia in primate studies," the investigators said.

The phase 1/2, first-in-human, dose-escalation and dose-expansion study will enroll up to 390 patients with HER2-expressing or HER2-amplified advanced solid tumors who have exhausted the potential for treatment with approved anti-HER2 treatments. Patients will receive BDC-1001 with or without an immune checkpoint inhibitor targeting PD-1.

The dose-escalation phase of the trial will help to determine safety and tolerability of the treatment and establish the phase 2 dose of BDC-1001 as monotherapy and in combination with an immune checkpoint inhibitor. Primary end points include incidence of adverse events, dose-limiting toxicities, and potential immune-related toxicities.

Patients will receive BDC-1001 intravenously every 3 weeks in increasing doses. The completion of the safety data portion of the trial will allow investigators to proceed with the immune checkpoint inhibitor combination component. The dose-expansion portion of the trial will evaluate both the monotherapy with BDC-1001 and the investigational agent in combination with a checkpoint inhibitor. The primary end point of the dose-expansion portion is overall response rate.

The investigators also hope to elucidate the mechanism of action for BDC-1001 and identify biomarkers to help improve selection of patients most likely to benefit from the treatment with and without checkpoint inhibitors.

Dumbrava EI, Sharma MR, Carvajal RD, et al. Phase 1/2 study of a novel HER2 targeting TLR7/8 immune-stimulating antibody conjugate (ISAC), BDC-1001, as a single agent and in combination with an immune checkpoint inhibitor in patients with advanced HER2-expressing solid tumors. Presented at: SABCS; December 8-11, 2020. Abstract OT-03-02. www.sabcs.org/portals/sabcs2016/2020%20SABCS/Final%20PDF%20Docs%20111620_All%20PDF%20File%20No%20Embargoed%20Abstracts.pdf

Investigators explained the potential for durable antitumor efficacy in patients with human epidermal growth factor receptor 2 (HER2)-expressing or -driven tumors who have exhausted other treatment options.

Latest Conference Articles